Researcher: Khodadust, Rouhollah
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Khodadust, Rouhollah
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Publication Metadata only Folic acid-conjugated cationic Ag2S quantum dots for optical imaging and selective doxorubicin delivery to HeLa cells(Future Medicine Ltd, 2017) Erkısa, Merve; Arı, Ferda; Ulukaya, Engin; N/A; Department of Chemistry; Department of Chemistry; Duman, Fatma Demir; Khodadust, Rouhollah; Acar, Havva Funda Yağcı; PhD Student; Other; Faculty Member; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Science and Engineering; College of Sciences; College of Sciences; N/A; N/A; 178902We aim to develop folic acid ( FA)-conjugated cationic Ag2S near-infrared quantum dots (NIRQDs) for the delivery of doxorubicin (DOX) selectively to folate receptor (FR)-positive cancer cells to achieve enhanced drug efficacy and optical tracking in the NIR region. Materials & methods: Cationic Ag2S NIRQDs were decorated with FA using a PEG bridge and loaded with DOX. In vitro studies were performed on FR-positive human cervical carcinoma cells and FR-negative A549 cells. Results: Significantly higher uptake of DOX by human cervical carcinoma cells cells and a greater therapeutic effect along with a strong intracellular optical signal were obtained with DOX-loaded FA-conjugated Ag2S NIRQDs. Conclusion: These Ag2S NIRQDs are promising theranostic nanoparticles for receptor-mediated delivery of DOX with enhanced drug efficacy combined with optical imaging.Publication Metadata only Blood-brain barrier dynamics of nanotechnological drug carriers in animal model of temporal lobe epilepsy(2017) Yılmaz, Canan Uğur; Orhan, Nurcan; Temizyürek, Arzu; Arıcan, Nadir; Küçük, Mutlu; Gürses, Candan; Ahıshalı, Bülent; Emik, Serkan; N/A; N/A; Department of Chemistry; N/A; Atış, Müge; Akcan, Uğur; Khodadust, Rouhollah; Kaya, Mehmet; PhD Student; PhD Student; Other; Faculty Member; Department of Chemistry; Graduate School of Health Sciences; Graduate School of Health Sciences; College of Sciences; School of Medicine; Koç University Hospital; 346431; N/A; N/A; 10486N/APublication Metadata only Blood-brain barrier dynamics of nanotechnological drug carriers in animal model of temporal lobe epilepsy(Wiley, 2018) Yilmaz, C. U.; Orhan, N.; Temizyurek, A.; Arican, N.; Kucuk, M.; Gurses, C.; Ahishali, B.; Emik, S.; N/A; N/A; N/A; Department of Chemistry; Atış, Müge; Akcan, Uğur; Kaya, Mehmet; Khodadust, Rouhollah; PhD Student; PhD Student; Faculty Member; Other; Department of Chemistry; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; College of Sciences; 346431; N/A; 10486; N/AN/APublication Metadata only Preclinical characterization of a novel palladium complex as anticancer drug candidate(Wiley, 2016) Erim, S. Durmuş; İçsel, Ceyda; Yılmaz, Veysel Turan; Ulukaya, Engin; Şahin, Önder; N/A; Department of Chemistry; Department of Chemistry; Ünal, Özlem; Khodadust, Rouhollah; Acar, Havva Funda Yağcı; PhD Student; Other; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; 178902N/APublication Metadata only Etoposide loaded SPION-PNIPAM nanoparticles improve thein vitrotherapeutic outcome on metastatic prostate cancer cells via enhanced apoptosis(Wiley-V C H Verlag Gmbh, 2020) Erkısa, Merve; Arı, Ferda; Ulukaya, Engin; Department of Chemistry; Department of Chemistry; N/A; Department of Chemistry; Ülkü, İrem; Khodadust, Rouhollah; Yar, Yasemin; Acar, Havva Funda Yağcı; Undergraduate Student; Other; PhD Student; Faculty Member; Department of Chemistry; College of Sciences; College of Sciences; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A; 178902Prostate cancer is among the leading causes of death worldwide because its metastatic form is a deadly disease. Therefore, the development of new chemotherapeutics is of immense importance. Nanoparticle technology seems to provide diverse options in this regard. Therefore, poly(N-isopropylacrylamide) (PNIPAM) coated superparamagnetic iron oxide nanoparticles (SPION) loaded with Etoposide were prepared in small sizes (57 nm) and with 3.5 % drug content to improve the efficiency of Etoposide in prostate cancer therapy. Sustained release of the drug was achieved, which found to be sensitive to low pH and high temperature. The anti-growth activity of SPION-PNIPAM-Etoposide formulation against metastatic prostate cancer cells (PC-3, LNCaP) were investigated by SRB assay, then, confirmed by ATP assay. Mode of cell death was evaluated by using flow cytometry analyses. A significant improvement of nanoformulated drug was observed at 5-10 mu g/ml doses of the drug in both cell lines. More importantly, this formulation enhanced the cytotoxic effect of Etoposide on PC-3 cells, which is considered more resistant to Etoposide than LNCaP and reduced the IC(50)value by 55 % reaching to 4.5 mu g drug/ml, which is a very significant improvement in the literature. It was clearly shown that nanoformulated drug provided about 3-fold increases in caspase-dependent early apoptotic cells in PC-3 cells. The novel formulation seems to successfully cause cell death of especially PC-3 metastatic prostate cancer cells. It should therefore be taken into consideration for further animal studies as a novel potent anticancer agent.Publication Metadata only Development of tailored SPION-PNIPAM nanoparticles by ATRP for dually responsive doxorubicin delivery and MR imaging(Royal Society of Chemistry (RSC), 2018) Akkoç, Yunus; Utkur, Mustafa; Sarıtaş, Emine Ülkü; Gözüaçık, Devrim; N/A; Department of Chemistry; Department of Chemistry; Yar, Yasemin; Khodadust, Rouhollah; Acar, Havva Funda Yağcı; PhD Student; Other; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; 178902Biocompatible, colloidally stable and ultra-small Fe3O4 nanoparticles (SPIONs) coated with poly(N-isopropyl-acrylamide) (PNIPAM) were synthesized via surface-initiated ATRP (atom transfer radical polymerization) to prevent excessive aggregation of magnetic cores and interparticle crosslinking, and to provide control over polymer content. These SPION-PNIPAM nanoparticles (NPs) have a hydrodynamic size between 8 and 60 nm depending on the PNIPAM content, and hence are ultrasmall in size and have an LCST around 38 degrees C. They had a high drug-loading capacity reaching 9.6 wt% doxorubicin in the final composition. The Dox release studies revealed pH and temperature-dependent release, which was not reported for PNIPAM before. Release of Dox under physiological conditions was below 20%, but around 90% at 42 degrees C and pH 5. This dually responsive nature is very advantageous to increase the drug efficacy and reduce side-effects, simultaneously. The cytocompatability of the SPION-PNIPAM NPs and the influence of Dox delivery to cells were investigated via in vitro cell viability, apoptosis, DNA-damage and confocal microscopy studies. The NPs were shown to be highly cytocompatible and induce significant cell death due to Dox when loaded with the drug. Besides, it was seen that the polymeric content can be used as an additional factor in tuning the release kinetics. Lastly, these nanoparticles reduced the signal intensity significantly in the T2 mode, acting as a potential SPION-based contrast agent. Overall, here, we demonstrate the design of small, smart theranostic nanoparticles with high drug-loading capacity and pH-dependent temperature-sensitive release characteristics with the ability to generate contrast in MRI.Publication Metadata only Targeted delivery of lacosamide-conjugated gold nanoparticles into the brain in temporal lobe epilepsy in rats(Elsevier, 2020) Yılmaz, Canan Uğur; Emik, Serkan; Orhan, Nurcan; Arican, Nadir; Küçük, Mutlu; N/A; N/A; N/A; Department of Chemistry; N/A; N/A; N/A; Temizyürek, Arzu; Atış, Müge; Akcan, Uğur; Khodadust, Rouhollah; Gürses, Rabia Candan; Ahıshalı, Bülent; Kaya, Mehmet; Other; PhD Student; PhD Student; Other; Faculty Member; Faculty Member; Faculty Member; Department of Chemistry; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; College of Sciences; School of Medicine; School of Medicine; School of Medicine; 357912; 346431; N/A; N/A; 110149; 9509; 10486Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures, and currently available drugs may fail to provide a thorough treatment of the patients. The present study demonstrates the utility of glucose-coated gold nanoparticles (GNPs) as selective carriers of an antiepileptic drug, lacosamide (LCM), in developing a strategy to cross the blood-brain barrier to overcome drug resistance. Intravenous administration of LCM-loaded GNPs to epileptic animals yielded significantly higher nanoparticle levels in the hippocampus compared to the nanoparticle administration to intact animals. The amplitude and frequency of EEG-waves in both ictal and interictal stages decreased significantly after LCM-GNP administration to animals with TLE, while a decrease in the number of seizures was also observed though statistically insignificant. In these animals, malondialdehyde was unaffected, and glutathione levels were lower in the hippocampus compared to sham. Ultrastructurally, LCM-GNPs were observed in the brain parenchyma after intravenous injection to animals with TLE. We conclude that glucose-coated GNPs can be efficient in transferring effective doses of LCM into the brain enabling elimination of the need to administer high doses of the drug, and hence, may represent a new approach in the treatment of drug-resistant TLE.Publication Metadata only Discovery of an exceptionally strong luminescence of polyethyleneimine-superparamagnetic iron oxide nanoparticles(Wiley-V C H Verlag Gmbh, 2018) Erdem, Emre; Ow-Yang, Cleva W.; N/A; Department of Chemistry; Department of Chemistry; N/A; N/A; Department of Chemistry; Ünal, Özlem; Yurtsever, İsmail Ersin; Khodadust, Rouhollah; Yağcı, Mustafa Barış; Durmuşoğlu, Emek Göksu; Acar, Havva Funda Yağcı; PhD Student; Faculty Member; Other; Researcher; N/A; Faculty Member; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; College of Sciences; N/A; 7129; N/A; N/A; N/A; 178902Polyethyleneimine (PEI) is rarely recognized as a luminescent polymer but is frequently used for the production of cationic nanoparticles and tagged with an organic fluorophore to be tracked optically. Herein, a strongly luminescent, branched PEI-superparamagnetic iron oxide nanoparticle (bPEI-SPION) without a traditional fluorophore is reported. A tremendous enhancement (1200 times) in the weak blue luminescence of bPEI is achieved only if it is adsorbed on a SPION during the synthesis of nanoparticles, which is improved further upon protonation, irreversibly. This is quite unexpected since SPIONs are strong absorbers in the visible region. All reaction parameters, different synthetic methods, as well as protonation are studied as independent factors to understand the origin of such enhancement. Detailed spectroscopic analysis and density functional theory calculations indicate that partial amine oxidation and Fe3+ reduction takes place during the synthesis, which significantly contributes to the luminescence enhancement. In addition, PEI-SPION exhibits excitation wavelength dependent emission and maintains its magnetic properties.Publication Open Access Theranostic potential of self-luminescent branched polyethyleneimine-coated superparamagnetic iron oxide nanoparticles(Beilstein-Institut, 2022) N/A; Khodadust, Rouhollah; Acar, Havva Funda Yağcı; Ünal, Özlem; PhD Student; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; N/A; 178902; N/APolyethylenimine (PEI), which is frequently used for polyplex formation and effective gene transfection, is rarely recognized as a luminescent polymer. Therefore, it is usually tagged with an organic fluorophore to be optically tracked. Recently, we developed branched PEI (bPEI) superparamagnetic iron oxide nanoparticles (SPION@bPEI) with blue luminescence 1200 times stronger than that of bPEI without a traditional fluorophore, due to partial PEI oxidation during the synthesis. Here, we demonstrate in vitro dye free optical imaging and successful gene transfection with luminescent SPION@bPEI, which was further modified for receptor mediated delivery of the cargo selectively to cancer cell lines overexpressing the epidermal growth factor receptor (EGFR). Proapoptotic polyinosinic-polycytidylic acid sodium (PIC) was delivered to HeLa cells with SPION@bPEI and caused a dramatic reduction in the cell viability at otherwise non-toxic nanoparticle concentrations, proving that bPEI coating is still an effective component for the delivery of an anionic cargo. Besides, a strong intracellular optical signal supports the optically traceable nature of these nanoparticles. SPION@bPEI nanoparticles were further conjugated with Erbitux (Erb), which is an anti-EGFR antibody for targeting EGFR-overexpressing cancer cell lines. SPION@bPEI-Erb was used for the delivery of a GFP plasmid wherein the transfection was confirmed by the luminescence of the expressed gene within the transfected cells. Poor GFP expression in MCF7, a slightly better expression in HeLa, and a significant enhancement in the transfection of HCT116 cells proved a selective uptake and hence the targeting ability of Erb-tagged nanoparticles. Altogether, this study proves luminescent, cationic, and small SPION@bPEI nanoparticles as strong candidates for imaging and gene therapy.Publication Open Access Impact of reaction variables and PEI/L-cysteine ratio on the optical properties and cytocompatibility of cationic Ag2S quantum dots as NIR bio-imaging probes(Royal Society of Chemistry (RSC), 2016) Department of Chemistry; Duman, Fatma Demir; Khodadust, Rouhollah; Durmuşoğlu, Emek Göksu; Yağcı, Mustafa Barış; Acar, Havva Funda Yağcı; PhD Student; Other; Researcher; Department of Chemistry; College of Sciences; Graduate School of Sciences and Engineering; N/A; N/A; N/A; N/A; 178902Near-infrared emitting semiconductor quantum dots (NIRQDs) are popular fluorescent probes due to better penetration depth and elimination of tissue autofluorescence. Here, we demonstrate one pot aqueous synthesis of cytocompatible, strongly luminescent, cationic Ag2S NIRQDs utilizing a mixed coating composed of branched polyethyleneimine (PEI)-25 kDa and L-cysteine (Cys) as in vitro luminescent tags and in vivo optical imaging agents. Ultrasmall sizes, a clear first excitonic peak in the absorption spectra, relatively narrow emission peaks with maxima between 730 and 775 nm and a Stokes shift less than 100 nm were obtained. Lifetime measurements indicate excitonic and defect-related emissions. Interestingly, not the emission maxima but the intensity was influenced by the Cys amount more dramatically. PEI/Cys 60/40 mol ratio provided the highest quantum yield reported until now for Ag2S NIRQD (157%) emitting at such a short wavelength. Low molecular weight PEI failed to produce luminescent QDs. Cytotoxicity evaluation of the most strongly luminescing NIRQDs, revealed the PEI/Cys (mol mol(-1)) 50/50 composition as the non-toxic composition below 2.4 mu g Ag per mL concentration. Others had low-toxicity. In vitro microscopy experiments showed endosomal distribution of NIRQDs in Hela cells and strong NIR signal. In vivo imaging study demonstrated that Ag2S NIRQDs could effectively be used as strong optical imaging agents.